Recent investigations in the rheumatoid arthritis field have brought forward a number of promising new leads that may help us understand this disease. One of these is the finding of high levels of la positive T cells in the peripheral blood and especially the synovial fluid and tissue. These cells appear to represent antigen sensitized cells and their detailed study may reveal significant new antigens. The la positive cells will be isolated and their response to a battery of potentially important antigens evaluated. Another lead that we wish to exploit is the finding of T cells with anti-IgG receptors that may play a dominant regulatory role in the disease. We plan to define the character of these receptors with anti-idiotypic antisera and hybridoma antibodies and determine their composition. The high level of T cells of this type in certain rheumatoid arthritis patients may make this system a uniquely good one for general studies on T cell receptors for antigen. The possibility of obtaining human monoclonal antibodies from human hybridomas should prove of special utility for many of these studies. Such hybridomas producing rheumatoid factors have been obtained in preliminary studies and the extension of this work should add to our understanding of these and other antibodies in this disease. Mouse hybridoma antibodies defining idiotypic and cross idiotypic relationships among the rheumatoid factors should aid considerably in various in vitro studies on these proteins. The possibility that the rheumatoid factors relate to the important Fc receptors on macrophages and lymphocytes is an intriguing one which we wish to explore.